While this approach can be highly effective, it does require training, resources and ongoing (lifelong?) interventions (not unlike most other chronic diseases).
Now a rather comprehensive paper by Soleyman and colleagues from the University of Birmingham, Alabama, published in Obesity Reviews provides an overview of obesity management in primary care.
As readers are well aware, our body weight are tightly regulated by a complex neuroendocrine system and defends us agains weight loss through a multi-faceted physiological response to prevent further weight loss and restore body weight.
As the authors note,
“To maintain weightloss, individuals must adhere to behaviours that oppose these physiological adaptations and the other factorsfavouring weight regain. However, it is difﬁcult for peoplewith obesity to overcome physiology with behaviour over the long term. Common reasons for weight regain include decreased caloric expenditure, decreased self-weighing frequency, increased caloric intake, increased fat intake and eating disinhibition over time.”
The paper provides a succinct overview of the evidence supporting behavioural, medical and surgical obesity treatments.
It also reiterates the basic principles of obesity management as outlined in the various guidelines:
1. Obesity is a chronic disease that requires long-term management. It is important to approach patients with information regarding the health implications.
2. The goal of obesity treatment is to improve the health of the patient, and it is not intended for cosmetic purposes.
3. The cornerstone of therapy is comprehensive lifestyle intervention from informed PCPs or other healthcare professionals.
4. The initial goal of therapy is a weight loss of 5–10% in most patients, as this is sufﬁcient to ameliorate many weight-related complications. However, weight loss of ≥10% may be needed to improve certain weight-related complications, such as obstructive sleep apnoea.
5. Consideration should be given to the use of a weight-loss medication or possible bariatric surgery, as the addition of these treatment modalities to lifestyle therapy can promote greater weight loss and maintain the weight loss for a longer period of time.
6. It is important for clinicians to evaluate the patient for weight-related complications, that can be improved by weight loss, and to consider such patients for more aggressive treatment.
As for how to get more primary care clinics to actually implement these approaches, the authors note that,
“Primary care practitioners need to address the problem of obesity in their patients, just as they would with any other chronic condition such as hypertension or type 2 diabetes, and to ensure that their patients are aware of the health risks of obesity.”
Again something that the Canadian Obesity Network is working hard to promote in this country.
Earlier this week, Novo Nordisk, the maker of Victoza and Saxenda, announced top-line results from the LEADER trial, which investigated the cardiovascular safety of liraglutide 1.8mg over a period of up to 5 years in more than 9,000 adults with type 2 diabetes at high risk of major adverse cardiovascular events.
The trial compared the addition of either liraglutide 1.8 mg or placebo to standard care and apparently met the primary endpoint of showing non-inferiority as well as demonstrating superiority, with a significant reduction in cardiovascular risk.
According to the news release, liraglutide demonstrated superior reduction of major adverse cardiovascular events in the primary endpoint of the study (composite outcome of the first occurrence of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke), a reduction that that was derived from all three components of the endpoint.
The safety profile of liraglutide in LEADER was reported as, “generally consistent with previous liraglutide clinical studies”.
While it is hard to fully interpret the study, the detailed results of which will be reported at the American Diabetes Conference in a few months, this may well be a landmark trial both for diabetes but also for obesity medications.
Thus, although LEADER did not test the higher liraglutide 3 mg dose indicated for obesity, it is indeed reassuring that at least the liraglutide 1.8 mg dose indicated for diabetes, did not increase (and even decreased) the risk for cardiovascular complications.
This is of importance, as readers may be well aware that the history of anti-obesity medications is plagued with drugs that raised safety concerns regarding cardiovascular events.
Thus, while we await the full results of the LEADER trial, there appears hope for optimism that with liraglutide we may finally have a drug for the treatment of obesity that has a favourable cardiovascular safety profile.
That would be a landmark indeed.
Disclaimer: I have received honoraria as a consultant and speaker for Novo Nordisk
Yesterday, Zafgen released data from its phase 2b trial of beloranib in patients with severe obesity complicated by type 2 diabetes.
Zafgen recently announced that its phase 2b trial (ZAF-203) of the MetAP2 inhibitor beloranib in 152 patients with severe obesity complicated by type 2 diabetes.
Accompanying an impressive 12.7 and 13.5% weight loss on 1.8 mg and 1.2 mg beloranib (vs 3.1% for placebo), respectively.
Unfortunately, these results are marred by the ongoing concern over potential thrombogenic adverse effects.
Thus of the nine serious adverse events identified in eight patients during the trial, one was a pulmonary embolism in the 1.2 mg treatment group. A subsequent screening process (following the FDA’s partial clinical hold on the trial) identified silent pulmonay emboli in two additional patients in the beloranib treatment arms.
Currently Zafgen is working to better understand the potential mechanisms underlying the apparent thrombogenic risk as well as developing a risk-mitigation strategy (at least for studies in patients with Prader-Willi Syndrome) that would help resolve the complete clinical hold the FDA placed on the beloranib for now.
Thus, the future remains uncertain for what would otherwise certainly be a big step forward to fill the continuing gap of more effective medical treatments for obesity.
Disclaimer: I have received consulting honoraria from Zafgen, the makers of belanorib
Now a paper by Argyro Syngelaki and colleagues from the UK, published in the New England Journal of Medicine, suggests that the anti-diabetes drug metformin may limit weight gain in pregnant non-diabetic women with obesity and also reduce the incidence of pre-eclampsia.
The researchers randomised 450 pregnant women with a BMI greater than 35 and no diabetes to either metformin (3 g/day) or placebo from weeks 12-18 weeks of gestation till delivery in a double-blind fashion.
Among the 400 women who completed the study, those on metformin gained about 2 Kg less weight than the placebo group.
There was also an almost 75% decrease in the risk of developing preeclampsia.
Despite these effects, metformin did not significantly reduce the incidence of large-for-gestational-age babies or other adverse neonatal outcomes.
While these findings may be somewhat disappointing with regard to outcomes in the offspring, the reduction in pre-eclampsia is impressive and, if confirmed, could well be an interesting use of this compound in high-risk pregnancies.
With the increasing number of youth living with severe obesity and the lack of good conservative treatments, it is not surprising that the volume of bariatric surgery performed in adolescents is on the rise.
Now a study by Thomas Inge and colleagues, published in the New England Journal of Medicine, examines the efficacy and safety of bariatric surgery in teens.
The prospective study was conducted in 242 adolescents (mean age 17 y) undergoing Roux-en-Y gastric bypass (161 participants) or sleeve gastrectomy (67) at 5 US centres.
With the caveat that 15% of participants were lost to follow-up and laboratory data was missing in 24% of participants, the authors report that at 3 years, the mean weight had decreased by 27% with remission of type 2 diabetes in 95% of participants who had had the condition at baseline.
Other improvements in health included remission of abnormal kidney function occurred in 86%, remission of prediabetes in 76%, remission of elevated blood pressure in 74%, and remission of dyslipidemia in 66% of those who had these conditions.
On the other hand, surgery was not without risks.: 57% of participants developed iron deficiencies and 13% of participants required at least one additional intraabdominal operation.
Thus, despite significant health benefits and improvement in quality of life, patients do have to be carefully monitored for nutritional deficiencies.
Obviously, 3 years is not a long period in the life of an adolescent and it will certainly take far longer follow-up to determine the durability of these findings.
Also, there remain significant questions about the psychosocial impact that surgery may have (both positive and negative) on the further development of these young participants.
Nevertheless, till we have better conservative treatments for severe obesity it appears that bariatric surgery may well be a viable treatment option for this population.